Feline Chlamydia psittaci is the etiologic agent for a common conjunctual and respiratory disease of cats known as feline pneumonitis (FPn) (Baker, J. A. (1942) Science 96:475-476). This highly contagious disease is characterized by sneezing and coughing and is accompanied by mucopurulent ocular and nasal discharges (Baker, J. A. (1944) J. Exp. Med. 79:159-172). All age groups of cats are susceptible and although mortality is not great, infected kittens and older animals may become severely debilitated. Furthermore, because of its extreme communicability, FPn constitutes a major problem in pet hospitals, clinics and catteries, etc.
Feline Chlamydial infection, like chlamydial infections in other species which are clinically manifested by ocular disease, is not restricted to the conjunctival mucosa. For example, it has been shown that chlamydia inoculation into pathogen-free kittens produced conjunctivitis and rhinitis as well as positive identification of chlamydia in the superficial gastric mucosa (Gaillard, E. T. et al. (1984) Am. J. Vet. Res. 45:2314-2321). In another study, C. psittaci was recovered from a female cat with persistent genital tract infection, resulting from ocular rather than direct genital infection (Darougar, S. M. et al. (1977) pages 186-198 in D. Hobson and K. K. Holmes (Ed.) Nongonococcal Urethritis and Related Infections, American Society for Microbiology, Washington, D.C.). Persistent genital tract infection by C. psittaci is believed to be a cause of reproductive failure in catteries, however the mechanism of such failure is unclear. The mode of extraocular transmission and the contribution of extraocular infection to the persistence and pathology of feline chlamydial disease is unknown.
Vaccination studies with modified-live compositions has produced conflicting results. Modified live chlamydial vaccines in general have shown variable efficacy ranging from no protection (Cello, R. M. J., Am. Vet. Med. Assoc. 158:932-938, 1971) to partial protection (Shewen, P. E., et al., Can. J. Comp. Med. 44:244-251, 1980) to almost complete protection (McKercher, D. G., Am. J. Vet. Res. 13:557-561, 1952; Mitzel, J. R., and A. Strating, A.J. Vet. Res. 38:1381-1363, 1977; Kolar, J. R. and T. A. Rude, Feline Practice 7:47-50, 1977 and Vet Med. S.A. Clin. 76:1171-1173, 1981; Wills, J. M. et al., Infec. Immun. 55:2653-2657, 1987). However, in studies demonstrating vaccine efficacy, chlamydia was isolated in conjunctival swabs from vaccinated cats 24 days post challenge (Mitzel and Strating, 1977), 31 days post challenge (Kohler and Rude, 1977), and as late as 68 days post challenge (Wills et al., 1987) with sporadic isolations occurring between 3 and 8 months post challenge (Wills, J. M. Ph.D. thesis, University of Bristol, England, 1986). In addition, Wills et al. (1978) have demonstrated that excretion of chlamydia from vaccinated cats was actually prolonged when compared to the controls. No difference could be demonstrated between the vaccinates and controls in the amount of chlamydial shedding from the eyes or the transmission of the organism to the gastrointestinal and genital tracts.
Similar studies with inactivated chlamydial preparations produced mixed results. In one feline study where the efficacy of a killed preparation was evaluated, irradiated and crystal violet treated, purified yolk sac suspensions were described and used (McKercher, D. G., Am. J. Vet. Res. 13: 557-561, 1952). The induced protection was comparable to that of modified-live vaccines similarly purified, but was inferior to a modified-live crude yolk sac preparation. On the hand, comparative challenge studies conducted with four inactivated vaccine preparations and a commercial modified-live vaccine demonstrated that the inactivated preparations conferred virtually no protection against chlamydial infection in felines (Shewen, P. E. et al., Can. J. Comp. Med. 44: 244-251, 1980).
The egg yolk sac-propagated FPn used to prepare the known modified-live and inactivated preparations is also known to contain a large amount of a toxin (Hamre, D. et al., J. Infect. Dis. 74:206-211 (1944). Release of this toxin, lipopolysaccharide, or another unidentified antigen(s) onto the eye during FPn infection may contribute significantly to the pathogenesis of the ocular disease caused by this organism.
Because of the documented inability of prior modified live preparations to reduce shedding, and the probability that modified-live vaccinated infected animals could shed both the vaccine and field strains, with the concomitant risk of recombination, reactivation, and communication of disease to surrounding uninfected animals, the need exists for the development of safe, efficacious inactivated C. psittaci vaccines. Moreover, prior inactivated preparations have been unsuccessful or markedly inferior to modified-live preparations.